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Oxidative stress and inflammation in Parkinson's disease: is there a causal link?

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a dramatic loss of dopaminergic neurons in the substantia nigra (SN). Among the many pathogenic mechanisms thought to contribute to the demise of these cells, dopamine-dependent oxidative stress has classically taken center stage due to extensive experimental evidence showing that dopamine-derived reactive oxygen species and oxidized dopamine metabolites are toxic to nigral neurons. In recent years, however, the involvement of neuro-inflammatory processes in nigral degeneration has gained increasing attention. Not only have activated microglia and increased levels of inflammatory mediators been detected in the striatum of deceased PD patients, but a large body of animal studies points to a contributory role of inflammation in dopaminergic cell loss. Recently, postmortem examination of human subjects exposed to the parkinsonism-inducing toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), revealed the presence of activated microglia decades after drug exposure, suggesting that even a brief pathogenic insult can induce an ongoing inflammatory response. Perhaps not surprisingly, non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of developing PD. In the past few years, various pathways have come to light that could link dopamine-dependent oxidative stress and microglial activation, finally ascribing a pathogenic trigger to the chronic inflammatory response characteristic of PD.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Pharmacology, Danish University of Pharmaceutical Sciences, Jagtvej 160, 2200 Copenhagen, Denmark.

    Source

    Experimental neurology 193:2 2005 Jun pg 279-90

    MeSH

    Animals
    Anti-Inflammatory Agents
    Disease Models, Animal
    Dopamine
    Encephalitis
    Humans
    Microglia
    Mitochondria
    Models, Neurological
    Oxidative Stress
    Parkinson Disease

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    15869932

    Citation

    TY - JOUR T1 - Oxidative stress and inflammation in Parkinson's disease: is there a causal link? AU - Hald,Andreas, AU - Lotharius,Julie, PY - 2004/09/29/received PY - 2005/01/13/revised PY - 2005/01/19/accepted PY - 2005/5/5/pubmed PY - 2005/7/16/medline PY - 2005/5/5/entrez SP - 279 EP - 90 JF - Experimental neurology JO - Exp. Neurol. VL - 193 IS - 2 N2 - Parkinson's disease (PD) is a neurodegenerative disorder characterized by a dramatic loss of dopaminergic neurons in the substantia nigra (SN). Among the many pathogenic mechanisms thought to contribute to the demise of these cells, dopamine-dependent oxidative stress has classically taken center stage due to extensive experimental evidence showing that dopamine-derived reactive oxygen species and oxidized dopamine metabolites are toxic to nigral neurons. In recent years, however, the involvement of neuro-inflammatory processes in nigral degeneration has gained increasing attention. Not only have activated microglia and increased levels of inflammatory mediators been detected in the striatum of deceased PD patients, but a large body of animal studies points to a contributory role of inflammation in dopaminergic cell loss. Recently, postmortem examination of human subjects exposed to the parkinsonism-inducing toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), revealed the presence of activated microglia decades after drug exposure, suggesting that even a brief pathogenic insult can induce an ongoing inflammatory response. Perhaps not surprisingly, non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of developing PD. In the past few years, various pathways have come to light that could link dopamine-dependent oxidative stress and microglial activation, finally ascribing a pathogenic trigger to the chronic inflammatory response characteristic of PD. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/15869932/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(05)00036-1 ER -